There is great power in comparing several human tissue types across the continuum of malignancy to identify commonalities in their response to stress and their potential to generate genetic diversity and activate evolutionary forces. In this application, all four Projects will use the human cells described in this Shared Resource. The two tissue types we have chosen for our initial studies center on two ofthe most common tumor types in humans, breast and prostate tissues. Each is hormonally driven and represents the most important clinical problems in both their early and late stages of malignant transformation. Currently the cell of origin for various human tumors is unknown. In breast tumors, luminal cell markers are often expressed and investigators have long hypothesized that the majority oftumor cells originate from the luminal population. For several decades, and more recently with in depth molecular analysis, many stem cell characteristics have been detected in tumor cells and, correspondingly, investigators have postulated that adult stem cells represent the cell of tumor origin. Our Resource wili provide our Investigators with each relevant population of purified cells to determine if differential responses to stress and activation of evolutionary forces distinguish the different populations. Cells will be evaluated after growth in both 2-D and 3-D conditions.